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Status |
Public on Feb 10, 2019 |
Title |
Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells [ChIP-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The SWI/SNF chromatin remodeling complex is altered in ~20% of human cancers. ARID1A, a component of the SWI/SNF chromatin-remodeling complex, is the most frequently mutated epigenetic regulator in human cancers. Inactivation of the SWI/SNF complex is synthetically lethal with inhibition of EZH2 activity. EZH2 inhibitors are entering clinical trials for specific tumor types with SWI/SNF mutations. However, mechanisms of de novo or acquired resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated ovarian cancer cells.
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Overall design |
Parental TOV21G cell line and and resistant to EZH2 inhibitor GSK126 treatment clones were assayed by RNA-seq and BRG1 CHIP-seq
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Contributor(s) |
Zhang R, Wu S |
Citation(s) |
30297712 |
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Submission date |
Feb 10, 2018 |
Last update date |
Jan 06, 2020 |
Contact name |
Priyankara J Wickramasinghe |
E-mail(s) |
[email protected]
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Phone |
2154956837
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Organization name |
The Wistar Institute
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Department |
Bioinformatics
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Lab |
Genomics
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Street address |
3601 Spruce Street
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (2) |
GSM2991371 |
BRG1 binding in parental TOV21G cell line |
GSM2991372 |
BRG1 binding in resistant clone 3 of TOV21G cell line |
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This SubSeries is part of SuperSeries: |
GSE110450 |
Catalytic subunits switch drives resistance to EZH2 inhibitors in ARID1A-mutated cells |
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Relations |
BioProject |
PRJNA433733 |
SRA |
SRP132631 |